Induction of an immune response against dengue virus using the prime-boost approach

Abstract

The invention relates to methods for the induction of an immune response to dengue virus. The method of inducing an immune response against dengue virus comprises administration of a non-replicating immunogen followed by a boost with a tetravalent live attenuated viral vaccine. Another aspect of the inventive subject matter is a method of inducing an immune response against dengue virus using a heterologous prime-boost regimen with the priming immunogen comprising a DNA expression system, an adenovirus expression vector or a Venezuelan equine encephalitis virus replicon system and the boosting immunogen comprising the same without the DNA expression system. Each expression system contains DNA sequences encoding dengue viral proteins.

What is claimed is: 
     
         1 . A method of inducing an immune response to dengue virus comprising administering a priming dengue virus immunogen and boosting with a heterologous dengue virus immunogen wherein:
 a. said priming dengue virus immunogen is selected from the group consisting of:
 i) a DNA expression system; 
 ii) an adenovirus expression vector; and 
 iii) a Venezuelan equine encephalitis virus replicon system; 
   b. said boosting dengue virus immunogen is selected from the group consisting of:
 i) an adenovirus expression vector; and 
 ii) a Venezuelan equine encephalitis virus replicon system. 
   
     
     
         2 . The method of  claim 1 , wherein said priming immunogen is composed of one or more adenovirus expression systems with each of said adenovirus systems containing DNA encoding pre-membrane and envelop genes from one or more strains selected from the group consisting of Dengue serotypes 1-4. 
     
     
         3 . The method of  claim 1 , wherein said priming immunogen is composed of one or more DNA expression systems with each of said DNA systems containing DNA encoding dengue virus pre-membrane and envelop genes from one or more strains selected from the group consisting of Dengue serotypes 1-4. 
     
     
         4 . The method of  claim 1 , wherein said priming immunogen is composed of one or more Venezuelan equine encephalitis virus replicon systems with each Venezuelan system containing DNA encoding dengue virus pre-membrane and envelop genes from one or more strains selected from the group consisting of Dengue serotypes 1-4. 
     
     
         5 . The method of  claim 1 , wherein said boosting immunogen is composed of one or more adenovirus expression systems with each of said adenovirus system containing DNA encoding pre-membrane and envelop genes from dengue strain other than that used in the priming dose. 
     
     
         6 . The method of  claim 1 , wherein said boosting immunogen is composed of one or more Venezuelan equine encephalitis virus replicon systems with each of said Venezuelan system containing DNA encoding dengue virus pre-membrane and envelop genes from dengue strains other than of the priming dose.